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3. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

Author

Xiao, Yinghong, Dolan, Patrick Timothy, Goldstein, Elizabeth Faul, Li, Min, Farkov, Mikhail, Brodsky, Leonid, and Andino, Raul

Subjects
Cell Line, COS Cells, Cell Line, Tumor, Hela Cells, Animals, Mice, Transgenic, Mice, Knockout, Cercopithecus aethiops, Humans, Poliovirus, Poliomyelitis, Interferons, Viral Nonstructural Proteins, Antiviral Agents, Gene Expression Profiling, Evolution, Molecular, Virulence, Organ Specificity, Mutation, Host-Pathogen Interactions, Immunity, Innate, Chlorocebus aethiops, HeLa Cells, Tumor, Mice, Transgenic, Knockout, Evolution, Molecular, Immunity, Innate
Abstract

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

Published
2017

6. RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence

Author

Xiao, Yinghong, Rouzine, Igor M, Bianco, Simone, Acevedo, Ashley, Goldstein, Elizabeth Faul, Farkov, Mikhail, Brodsky, Leonid, and Andino, Raul

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Biotechnology, Emerging Infectious Diseases, Infectious Diseases, Genetics, Biodefense, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Adaptation, Physiological, Animals, DNA-Directed RNA Polymerases, Evolution, Molecular, Humans, Poliomyelitis, Poliovirus, RNA, Viral, Recombination, Genetic, Selection, Genetic, Viral Proteins, Virulence, Virus Replication, Microbiology, Immunology, Biochemistry and cell biology, Medical microbiology
Abstract

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations.

Published
2016

7. Unveiling SEER-CAHPS®: A New Data Resource for Quality of Care Research

Author

Chawla, Neetu, Urato, Matthew, Ambs, Anita, Schussler, Nicola, Hays, Ron D, Clauser, Steven B, Zaslavsky, Alan M, Walsh, Kayo, Schwartz, Margot, Halpern, Michael, Gaillot, Sarah, Goldstein, Elizabeth H, and Arora, Neeraj K

Subjects
Health Services and Systems, Health Sciences, Health Services, Cancer, Aging, Clinical Research, Prevention, 8.1 Organisation and delivery of services, 2.4 Surveillance and distribution, Good Health and Well Being, Aged, Databases, Factual, Female, Health Services Research, Humans, Male, Medicare, Middle Aged, National Cancer Institute (U.S.), Patient Satisfaction, Program Evaluation, Quality Assurance, Health Care, SEER Program, United States, patient experiences, cancer, chronic disease, data linkage, Medicare claims, quality of care, CAHPS, SEER registry, Clinical Sciences, General & Internal Medicine, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundSince 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care.ObjectiveTo describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS®) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data.DesignThis is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care.ParticipantsIn total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort.Main measuresThe data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys.Key resultsSizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage.ConclusionsSEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experiences of care across different diagnoses and treatment modalities, and enables comparisons by type of insurance.

Published
2015

12. Do Hospital Characteristics Predict Racial-and-Ethnic Disparities in Patient Experience? National Results from the HCAHPS Survey

Author

Beckett, Megan K., primary, Elliott, Marc N., additional, Hambarsoomian, Katrin, additional, Tamayo, Loida, additional, Lehrman, William G., additional, Agniel, Denis, additional, Khau, Meagan, additional, Goldstein, Elizabeth, additional, Giordano, Laura A., additional, Ng, Judy H., additional, and Martino, Steven C., additional

Published
2023
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16. Inpatient care experiences differ by preferred language within racial/ethnic groups

Author

Quigley, Denise D., Elliott, Marc N., Hambarsoomian, Katrin, Wilson-Frederick, Shondelle M., Lehrman, William G., Agniel, Denis, Ng, Judy H., Goldstein, Elizabeth H., Giordano, Laura A., and Martino, Steven C.

Subjects
Comparative analysis, Social aspects, Surveys, Patient care -- Comparative analysis -- Social aspects, Medical care quality -- Comparative analysis -- Social aspects, African Americans -- Surveys -- Comparative analysis -- Social aspects, Hispanic Americans -- Surveys -- Comparative analysis -- Social aspects, Native Americans -- Surveys -- Comparative analysis -- Social aspects, Hospitals -- Comparative analysis -- Social aspects, Hospital patients -- Surveys -- Comparative analysis -- Social aspects, Minorities, Regression analysis
Abstract

1 | INTRODUCTIONFor the 65.5 million U.S. residents who speak languages other than English at home, (1,2) health and health care may be compromised by difficulty in communicating their medical [...], Objective: To describe differences in patient experiences of hospital care by preferred language within racial/ethnic groups.Data Source: 2014-2015 HCAHPS survey data.Study Design: We compared six composite measures for seven languages (English, Spanish, Russian, Portuguese, Chinese, Vietnamese, and Other) within applicable subsets of five racial/ethnic groups (Hispanics, Asian/Pacific Islanders, American Indian/Alaska Natives, Blacks, and Whites). We measured patient-mix adjusted overall, between- and within-hospital differences in patient experience by language, using linear regression.Data Collection Methods: Surveys from 5 480 308 patients discharged from 4517 hospitals 2014-2015.Principal Findings: Within each racial/ethnic group, mean reported experiences for non-English-preferring patients were almost always worse than their English-preferring counterparts. Language differences were largest and most consistent for Care Coordination. Within-hospital differences by language were often larger than between-hospital differences and were largest for Care Coordination. Where between-hospital differences existed, non-English-preferring patients usually attended hospitals whose average patient experience scores for all patients were lower than the average scores for the hospitals of their English-preferring counterparts.Conclusions: Efforts should be made to increase access to better hospitals for language minorities and improve care coordination and other facets of patient experience in hospitals with high proportions of non-English-preferring patients, focusing on cultural competence and language-appropriate services.KEYWORDSpatient assessment, quality of care (measurement), survey research

Published
2019
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17. Medicare Advantage and Fee-for-Service Performance on Clinical Quality and Patient Experience Measures: Comparisons from Three Large States

Author

Timbie, Justin W., Bogart, Andy, Damberg, Cheryl L., Elliott, Marc N., Haas, Ann, Gaillot, Sarah J., Goldstein, Elizabeth H., and Paddock, Susan M.

Subjects
Quality management, Health care industry, Medicare -- Quality management, Health maintenance organizations -- Quality management
Abstract

Thirty-three percent of Medicare beneficiaries were enrolled in a Medicare Advantage (MA) health plan in 2016, or nearly 17.6 million Medicare beneficiaries (Jacobson et al. 2017). The MA program, which [...], Objective. To compare performance between Medicare Advantage (MA) and Fee-for-Service (FFS) Medicare during a time of policy changes affecting both programs. Data Sources/Study Setting. Performance data for 16 clinical quality measures and 6 patient experience measures for 9.9 million beneficiaries living in California, New York, and Florida. Study Design. We compared MA and FFS performance overall, by plan type, and within service areas associated with contracts between CMS and MA organizations. Case mix-adjusted analyses (for measures not typically adjusted) were used to explore the effect of case mix on MA/FFS differences. Data Collection/Extraction Methods. Performance measures were submitted by MA organizations, obtained from the nationwide fielding of the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) Survey, or derived from claims. Principal Findings. Overall, MA outperformed FFS on all 16 clinical quality measures. Differences were large for HEDIS measures and small for Part D measures and remained after case mix adjustment. MA enrollees reported better experiences overall, but FFS beneficiaries reported better access to care. Relative to FFS, performance gaps were much wider for HMOs than PPOs. Excluding HEDIS measures, MA/FFS differences were much smaller in contract-level comparisons. Conclusions. Medicare Advantage/Fee-for-Service differences are often large but vary in important ways across types of measures and contracts. Key Words. Medicare Advantage, quality measurement, quality of care, patient experience, case mix adjustment

Published
2017
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22. Accelerating improvement and narrowing gaps: trends in patients' experiences with hospital care reflected in HCAHPS public reporting

Author

Elliott, Marc N., Cohea, Christopher W., Lehrman, William G., Goldstein, Elizabeth H., Cleary, Paul D., Giordano, Laura A., Beckett, Megan K., and Zaslavsky, Alan M.

Subjects
United States. Centers for Medicare and Medicaid Services -- Services, Surveys, Services, Health care industry, Health care industry -- Surveys, Patient satisfaction -- Surveys
Abstract

In 1995, the agency now called the Agency for Healthcare Research and Quality initiated the Consumer Assessment of Healthcare Providers and Systems (CAHPS) project to develop surveys and survey protocols [...], Objective. Measure HCAHPS improvement in hospitals participating in the second and fifth years of HCAHPS public reporting; determine whether change is greater for some hospital types. Data. Surveys from 4,822,960 adult inpatients discharged July 2007 June 2008 or July 2010-June 2011 from 3,541 U.S. hospitals. Study Design. Linear mixed-effect regression models with fixed effects for time, patient mix, and hospital characteristics (bedsize, ownership, Census division, teaching status, Critical Access status); random effects for hospitals and hospital-time interactions; fixed-effect interactions of hospital characteristics and patient characteristics (gender, health, education) with time predicted HCAHPS measures correcting for regression-to-the-mean biases. Data Collection Methods. National probability sample of adult inpatients in any of four approved survey modes. Principal Findings. HCAHPS scores increased by 2.8 percentage points from 2008 to 2011 in the most positive response category. Among the middle 95 percent of hospitals, changes ranged from a 5.1 percent decrease to a 10.2 percent gain overall. The greatest improvement was in for-profit and larger (200 or more beds) hospitals. Conclusions. Five years after HCAHPS public reporting began, meaningful improvement of patients' hospital care experiences continues, especially among initially low-scoring hospitals, reducing some gaps among hospitals. Key Words. HCAHPS, for-profit, improvement, bedsize

Published
2015
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26. Impurity and gender in the Hebrew Bible : ideological intersections in the books of Leviticus, Ezekiel and Ezra

Author

Goldstein, Elizabeth Wayne

Subjects
UCSD Dissertations, Academic History. (Discipline), Biblical teaching Purity Ritual, History of doctrines Judaism Purity Ritual, Ethics in the Bible, Women in the Bible, Biblical teaching Women, Menstruation Religious aspects Judaism, Biblical teaching Sin
Abstract

The central argument of my dissertation is based on two bodies of literature. The first area deals with the categorization of biblical impurity and is articulated most effectively by Jonathan Klawans. Klawans demonstrates that there are two ideologies of purity in the Hebrew Bible, ritual and moral. The state of ritual impurity pertains to the human body, is unavoidable, temporary and can be cleansed. Conversely, moral impurity is incurred through behavioral choice. Three grave sins cause moral impurity : murder, violation of sexual prohibitions, and apostasy. No purifying activities can reverse the impurity. Moral impurity, unlike ritual impurity, has severe consequences. Either the land will expel its inhabitants or violators will be subject to krt, being cut off from their people. I have also based my argument on source critical scholarship and linguistic studies that demonstrates that priestly writing predates the writing of the exilic prophet Ezekiel. I show that Ezekiel distorts priestly ideas about women and their blood by intentionally confusing the categories of ritual and moral impurity. Furthermore, in the still later book of Ezra- Nehemiah, the word ndh, a term that previously referred only to menstruation, a cause of ritual impurity, has now come to refer to the general contamination of moral impurity. In Ezra, this transition has occurred, perhaps, unbeknownst to its author. Thus, there is a correlation between the ideologies of impurity in the Bible (ritual and moral) and an increasingly negative portrayal of women and their bodies. For prophetic writers, moral impurity became an effective way to speak about the experience of exile (586/7-530). The deity literally expelled the people for their sins. To the detriment of women, a regularly occurring bodily function, which even the pre-exilic priestly writers viewed as normative, became the symbol of the people's gravest transgressions

Published
2010

27. State policy choices and Medicaid long-term care expenditures

Author

Miller, Nancy A., Harrington, Charlene, Ramsland, Sarah, and Goldstein, Elizabeth

Subjects
Medicaid -- Finance, Community health services -- Management, Medical care, Cost of -- Models, Psychology and mental health, Seniors
Abstract

State long-term care policies are directed toward a variety of goals. Concerns with expenditure control are primary. Certain states are also seeking to increase the availability of community-based care. A more balanced system would assist consumers in attaining valued goals, while being consonant with federal policy initiatives and legal rulings. The authors examine the relationship between state policies and Medicaid long-term care expenditures. These relationships are tested by multiple regression analysis, using a random effects model for 1991 through 1997. Prospective payment may moderate nursing facility expenditure growth and total long-term care expenditures. Institutional supply constraints demonstrated a positive relationship to both forms of community-based care expenditures. The authors found no evidence of Medicare maximization as a policy to constrain Medicaid expenditure growth. Finally, the authors note the importance of additional work in exploring the dynamics between state long-term care policies and expenditures for individuals with differing disabilities.

Published
2002

33. Synthesis of Enantioenriched (Poly)Fluorinated Building Blocks, 2,2-Disubstituted Pyrrolidines and [7,7]Paracyclophanes

Author

Goldstein, Elizabeth Lee

Subjects
Chemistry, FOS: Chemical sciences, Alkaloid, Organic Chemistry, Paracyclophane, Asymmetric Allylic Alkylation, Natural Product Total Synthesis
Abstract

The Stoltz group, and moreover the synthetic community at large, has long been interested in the synthesis of enantioenriched compounds with interesting biological activities. This thesis presents three projects unified in an attempt to access compounds with relevance to the medicinal chemistry and natural products communities, encompassing reaction development, synthetic strategy and natural product synthesis. A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed allylic alkylation is described. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents. The synthesis of a variety of enantioenriched 2,2-disubstituted pyrrolidines is described. A stereogenic quaternary center is first formed utilizing an asymmetric allylic alkylation reaction of a benzyloxy imide, which can then be reduced to a chiral hydroxamic acid. This compound can then undergo a thermal "Spino" ring contraction to afford a carbamate protected 2,2-disubstituted pyrrolidine stereospecifically, allowing access to new molecules that could be useful in the medicinal chemistry community. Finally, we have developed a synthesis of an enaptioenriched [7,7]paracyclophane compound using sequential C-H functionalization reactions, including selective Rh-catalyzed C-H insertion reactions developed by the Davies group at Emory University. Investigations are currently ongoing into potential antimicrobial activity of different [7,7]paracyclophanes and the total synthesis of naturally occurring [7,7]paracyclophanes.

Published
2020
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37. Park Row

Author

Goldstein, Elizabeth and McKinney, Charles

Published
1994

38. Lessons learned from the National Medicare & You Education Program

Author

Goldstein, Elizabeth, Teichman, Lori, Crawley, Barbara, Gaumer, Gary, Joseph, Catherine, and Reardon, Leo

Subjects
Aged -- Care and treatment, Medicare -- Finance, Information services industry -- Finance, Information services -- Finance, Medical care, Balanced Budget Act of 1997, Business, Health care industry, Company financing, Information services industry, Finance, Care and treatment
Abstract

In fall 1998 CMS implemented the National Medicare Education Program (NMEP) to educate beneficiaries about their Medicare program benefits; health plan choices; supplemental health insurance; beneficiary rights, responsibilities, and protections; and health behaviors. CMS has been monitoring the implementation of the NMEP in six case study sites as well as monitoring each of the information channels for communicating with beneficiaries. This article describes select findings from the case studies, and highlights from assessment activities related to the Medicare & You handbook, the toll-free 1-800-MEDICARE Helpline, Internet, and Regional Education About Choices in Health (REACH)., INTRODUCTION The Balanced Budget Act (BBA) of 1997 mandated the most significant changes to Medicare since its inception. One of these changes was the expansion of health insurance options by [...]

Published
2001

39. CMS's consumer information efforts

Author

Goldstein, Elizabeth

Subjects
United States. Centers for Medicare and Medicaid Services, Aged -- Care and treatment, Medicare, Medicaid, Information services industry, Information services, Information services industry, Business, Health care industry
Abstract

INTRODUCTION AND BACKGROUND In this issue of the Health Care Financing Review, we focus on consumer information for the Medicare population. Over the last several years the Centers for Medicare [...]

Published
2001

40. Palladium-Catalyzed Enantioselective C_(sp)^3–C_(sp)^3 Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks

Author

Lu, Yanhui, Goldstein, Elizabeth L., and Stoltz, Brian M.

Abstract

A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed decarboxylative allylic alkylation is described. The stereoselective C_(sp)^3–C_(sp)^3 cross-coupling reaction delivers five- and six-membered ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral centers in high yields and enantioselectivities. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents.

Published
2018

43. The Relationship between Written Coherence and Thinking.

Author

Goldstein, Elizabeth Odoroff

Abstract

It was hypothesized that writers of sentence pairs with clear relationships would have better recall of second sentences than would writers of sentence pairs with unclear relationships. Clear connections between sentences in sentence pairs were defined as those sentences in which the language of the first sentence was explicitly picked up in the second sentence to fulfill a "given/new" contract. In each of ten papers used in the study, three pairs of connected sentences were selected that honored the given/new contract, as were two pairs of unconnected sentences violating the given/new framework. The central task in the study was for the writers of the term papers to try to remember the second sentence in each pair. Analyses showed that the ten writers tended to remember the second sentence of pairs with clear connections, but not the second sentence of pairs with unclear connections. Writers whose sentences were usually clearly connected had a better memory for clear connections than for unclear connections. Thus, the research demonstrated relationships between the structure of a writer's language and memory for that language, supporting the idea that the nature of the connections between sentences may be closely linked to the thinking processes of the writer. (RL)

Published
1980

44. Connections, Coherence, and Cognition in Composition.

Author

Goldstein, Elizabeth and Perfetti, Charles

Abstract

In a study conducted to show the importance of sentence connections as a way of looking at a writer's cognitive processes, three devices used to achieve coherence in written discourse were compared and proved to be unequally effective. The devices were cohesion (use of a textual reference in a sentence that has an antecedent in a preceding sentence), major argument overlap (use of a reference that is a relational concept to a proposition in a preceding sentence), and the given/new obligation that requires that each sentence convey two kinds of information-given information and new information. Given information is information writers believe readers already know either from prior knowledge or from preceding sentences. New information is information writers believe readers do not yet know or are not thinking about until writers call attention to it. This given/new obligation demands that the writer arrange material so that readers' expectations are fulfilled. Since subjects in the study did not remember sentences that had only major argument overlap and textual cohesion, it was concluded that in the absence of shared prior knowledge, the fulfillment of the given/new obligation is necessary for coherence. (AEA)

Published
1980

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